Response variability to aspirin and one-year prediction of vascular events in patients with stable coronary artery disease

The aim of this study was to assess the association between “aspirin non responsiveness” in patients with coronary artery diseases (CAD) and the risk of major adverse cardiovascular events (MACE). 204 patients with CAD receiving aspirin (250 mg/d) were included. Both Collagen/Epinephrine Closure Time (CEPI-CT) and urinary Thromboxane B2 (uTxB2) concentration was used to determine the patients aspirin responsiveness. The clinical primary endpoint was the occurrence of MACE including: cardiovascular death, MI, stroke or transient ischemic attack. The secondary endpoint was the occurrence of Recurrent Acute Vascular Event (RAVE: MI, stroke or transient ischemic attack). After 1-year follow-up, no responders diagnosed by CEPI-CT had a trend for higher risk of MACE (13% vs 7.4%; P = 0.22) and significant higher risk of RAVE (OR = 2.1; 95%CI: 1.7–2.4; P = 0.01) when compared to good responders. Multivariate analysis showed that CEPI-CT < 143 s was the only independent predictor of RAVE (OR = 6.3; 95% CI: 1.2–32.2; P = 0.026). Aspirin non-responsiveness, diagnosed by the uTxB2, was not associated with an increased risk of either MACE or RAVE. Our results, reinforce the importance of being able to diagnose laboratory “aspirin non responsiveness”, and extend the evidence that aspirin non responsiveness may explain in part the occurrence of RAVE.     

Appropriateness of coronary revascularization in patients with stable coronary artery disease:a multicenter clinical trial

<正>Objective To assess the appropriateness of coronary revascularization in patients with stable coronary artery disease(CAD).Methods We conducted a multi-center,cross-sectional study involving stable CAD patients with coronary lesion stenosis≥50% in 4 heart centers.The appropriateness of coronary revascularization was     

Cardioprotection by resveratrol: A human clinical trial in patients with stable coronary artery disease

Several beneficial effects of resveratrol (RES), a natural antioxidant present in red wine have already been described. The aim of our study was to investigate if RES had a clinically measurable cardioprotective effect in patients after myocardial infarction. In this double-blind, placebo controlled trial 40 post-infarction Caucasian patients were randomized into two groups. One group received 10 mg RES capsule daily for 3 months. Systolic and diastolic left ventricular function, flow-mediated vasodilation (FMD), several laboratory and hemorheological parameters were measured before and after the treatment. Left ventricular ejection fraction showed an increasing tendency (ns) by RES treatment. However, left ventricular diastolic function was improved significantly (p < 0.01) by RES. A significant improvement in endothelial function measured by FMD was also observed (p < 0.05). Low-density lipoprotein (LDL) level significantly decreased (p < 0.05) in the RES treated group. Red blood cell deformability decreased and platelet aggregation increased significantly in the placebo group (p < 0.05), while resveratrol treatment has prevented these unfavourable changes. Concerning other measured parameters no significant changes were observed neither in placebo nor in RES group. Our results show that resveratrol improved left ventricle diastolic function, endothelial function, lowered LDL-cholesterol level and protected against unfavourable hemorheological changes measured in patients with coronary artery disease (CAD).     

Clinical relevance of aspirin resistance in patients with stable coronary artery disease: a prospective follow-up study (PROSPECTAR).

Aspirin resistance may increase the risk of major adverse cardiac events (MACE) more than threefold in patients with stable coronary artery disease (CAD). This study aimed to determine the prevalence of aspirin resistance in patients with stable CAD, the role of aspirin resistance on outcome in the follow-up, and the effect of clopidogrel therapy in MACE prevention in aspirin-resistant individuals. We detected the prevalence of aspirin resistance in 234 patients with stable CAD. Platelet function was determined by PFA-100 with collagen and/or epinephrine and collagen and/or ADP cartridges. The mean follow-up time was 20.6 +/- 6.9 months. The primary endpoints of the study were occurrence of myocardial infarction, unstable angina, stroke and cardiac death. Of patients, 22.2% (n = 52) were aspirin resistant by PFA-100. During follow-up, MACE occurred in eight patients (15.4%) with aspirin resistance and in 20 patients (11.0%) with aspirin-sensitive platelet aggregation (P = 0.269). MACE increased in aspirin-resistant patients after termination of clopidogrel therapy. Eleven patients experienced MACE after cessation of clopidogrel therapy (P < 0.001). The MACE risk in patients with stable CAD having detected aspirin resistance was similar compared with patients having aspirin-sensitive platelet aggregation by PFA-100. The MACE prevalence increased during follow-up, however, just after cessation of clopidogrel therapy.     

Iron status and clinical outcome in patients with coronary artery disease after coronary stenting

BACKGROUND AND AIM: So far, no studies have assessed whether there is an association between iron status and the incidence of major adverse cardiac events or restenosis after coronary stenting. We conducted this study to investigate whether there is an association between body iron status and clinical outcome in patients with coronary artery disease after coronary stenting. METHODS AND RESULTS: The study included 664 patients with coronary artery disease who underwent coronary stent implantation. The soluble transferring receptor/ferritin ratio (sTfR/ferritin ratio) was used as an index of iron status. Patients were divided into three groups according to the tertiles of sTfR/ferritin ratio: lower tertile (<11.9; n = 221), middle tertile (11.9-27.8; n = 221) and upper tertile (>27.8; n = 222). The combined incidence of major adverse cardiac events (death, myocardial infarction and target vessel revascularization) was the primary end point of the study. Patients in the lower tertile of the sTfR/ferritin ratio presented more often with unstable angina or acute myocardial infarction and had longer lesions and higher grade of stenosis than the patients in the middle or upper tertile of the sTfR/ferritin ratio. Angiographic restenosis at 6-month angiography was also evaluated. The cumulative event rate of composite end point of death, myocardial infarction or target vessel revascularization was 27.6% in patients in the lower tertile, 24.4% in patients in the middle tertile and 28.4% in patients in the upper tertile of the sTfR/ferritin ratio (p = 0.68). Restenosis was found in 27.8% (n = 45) in the lower tertile, 25.8% (n = 42) in the middle tertile and 27.5% (n = 38) in the upper tertile of the sTfR/ferritin ratio (p = 0.90). CONCLUSIONS: Our study showed no association between iron status and the incidence of major adverse cardiac events or angiographic coronary restenosis in patients with coronary artery disease after coronary stenting.     

Angina, coronary risk factors and coronary artery disease in patients with valvular disease. A prospective study

The relationship between coronary risk factors and coronaryartery disease in patients with valvular heart disease was studiedprospectively in 387 consecutive patients undergoing routinecoronary arteriography prior to valve replacement. Coronary artery disease was as common in patients with mitralvalve disease (31.9%) as in those with aortic valve disease(26.8%) Although it occurs more frequently in patients withangina (45.7%) significant coronary artery disease is foundin 19.2% (47 of 245) of those without angina (P<0.001), suggestingthat the presence of angina alone is an unreliable indicatorof significant coronary disease. The prevalence and severityof significant coronary artery disease increases progressivelyas the number of coronary risk factors also increase (P<0.001)but the prevalence is low (3%) in patients in whom both anginaand coronary risk factors are absent. These findings suggestthat preoperative coronary arteriography might be omitted inthis latter group of patients.     

Aspirin resistance and adverse clinical events in patients with coronary artery disease

Purpose

We sought to determine the clinical significance of aspirin resistance measured by a point-of-care assay in stable patients with coronary artery disease (CAD).

Methods

We used the VerifyNow Aspirin (Accumetrics Inc, San Diego, Calif) to determine aspirin responsiveness of 468 stable CAD patients on aspirin 80 to 325 mg daily for ≥4 weeks. Aspirin resistance was defined as an Aspirin Reaction Unit ≥550. The primary outcome was the composite of cardiovascular death, myocardial infarction (MI), unstable angina requiring hospitalization, stroke, and transient ischemic attack.

Results

Aspirin resistance was noted in 128 (27.4%) patients. After a mean follow-up of 379 ± 200 days, patients with aspirin resistance were at increased risk of the composite outcome compared to patients who were aspirin-sensitive (15.6% vs 5.3%, hazard ratio [HR] 3.12, 95% confidence intervals [CI], 1.65-5.91, P < .001). Cox proportional hazard regression modeling identified aspirin resistance, diabetes, prior MI, and a low hemoglobin to be independently associated with major adverse long-term outcomes (HR for aspirin resistance 2.46, 95% CI, 1.27-4.76, P = .007).

Conclusions

Aspirin resistance, defined by an aggregation-based rapid platelet function assay, is associated with an increased risk of adverse clinical outcomes in stable patients with CAD.     

Role of medical versus interventional strategies to prevent coronary events in patients with stable coronary artery disease

Chronic coronary artery disease (CAD) is a highly prevalent and complex health problem in the United States. The goals of treatment in patients with stable CAD are to reduce symptoms and thus improve quality of life, reduce myocardial ischemia, and, more importantly, reduce the risk of myocardial infarction and death. In this article, the authors review the evidence regarding the role of medical versus interventional strategies in reducing the risk of future coronary events in patients with stable CAD.     

Glucose metabolism in non-diabetic patients with stable coronary artery disease.

BACKGROUND: Diabetes and other forms of impaired glucose metabolism (IGM) can be present in patients with coronary artery disease (CAD), despite normal fasting glycemia and no prior evidence of diabetes. Undiagnosed IGM can be associated with increased risk of cardiovascular events. OBJECTIVE: To assess the prevalence of IGM in patients with CAD and without diabetes and to identify its repercussions on their cardiovascular risk profile. METHODS: Consecutive patients with CAD documented by angiography, without prior history of diabetes and fasting glycemia < 126 mg/dL, were studied. An oral glucose tolerance test (OGTT) was performed to identify and classify IGM. The patients were divided into three groups: normal if fasting glycemia < 100 mg/dL and normal OGTT; prediabetes if fasting glycemia > or = 100 mg/dL and abnormal OGTT, with 2-h glycemia > or = 140 and < 200 mg/dL; and diabetes if 2-h glycemia > or = 200 mg/dL after OGTT. For assessment of the cardiovascular risk profile, various clinical, laboratorial (including lipid profile, fasting insulinemia 2 h after OGTT, insulin resistance index and A1c hemoglobin) and angiographic characteristics were analyzed. The differences between groups were determined. RESULTS: 54 patients were studied (mean age 65 +/- 9 years, 78 % male) and IGM was identified in 37 (69%), with prediabetes in 23 (43%) and diabetes in 14 (26%). Patients with IGM had more dyslipidemia, higher levels of fasting glycemia, triglycerides and urea and lower HDL cholesterol. Metabolic syndrome was diagnosed in 12% of patients in the normal group, 44% in the prediabetes group and 50% in the diabetes group (p = 0.047). CAD was more severe in the presence of IGM, being multivessel in 84% of these patients versus 59% in the normal group (p = 0.046). CONCLUSION: In patients with CAD without clinical suspicion of diabetes, a routine OGTT can identify a significant percentage with prediabetes and diabetes, which can have a negative impact on their cardiovascular risk profile.     

Left atrioventricular plane displacement determined by echocardiography: a clinically useful, independent predictor of mortality in patients with stable coronary artery disease

BACKGROUND: Echocardiographically determined left atrioventricular plane displacement (AVPD) is strongly related to prognosis in patients with chronic heart failure and in postmyocardial infarction patients. We aimed at exploring whether AVPD, unlike ejection fraction, is related to mortality in patients with stable coronary artery disease (CAD). METHODS AND RESULTS: Atrioventricular plane displacement was assessed by two dimensionally guided M-mode echocardiography in the four and two chamber views, in 333 consecutive patients with stable CAD and an abnormal coronary angiogram. Patients were followed up for an average of 41 months. AVPD was lower in patients who died (n= 30, 9.0 %) compared with survivors (9.0 +/- 2.2 vs. 11.5 +/- 2.1 mm, P<0.0001). Amongst patients with prior myocardial infarction (n=184) AVPD was 8.7 +/- 2.3 mm in those who died (n=17) and 11.2 +/- 2.3 mm in the survivors (P<0.0001). In patients without prior myocardial infarction (n=149), AVPD was 9.4 +/- 2.1 (n=13) and 11.8 +/- 1.8 mm, respectively (P<0.0001). Age, AVPD and four other echocardiographical variables correlated significantly with prognosis in univariate logistic regression analysis. In multiple logistic regression analysis only AVPD (P<0.0001) correlated independently with mortality. CONCLUSION: Echocardiographically determined AVPDis a clinically useful, independent prognostic tool in patients with stable CAD. The presence of a documented previous myocardial infarction does not influence this observation.     

Detection of aspirin resistance by PFA-100: prevalence and aspirin compliance in patients with chronic stable angina

Most acute coronary syndromes result from a platelet-rich occlusion of the coronary arteries. Antiplatelet drugs are of proven efficacy in preventing myocardial infarction, unstable angina, and stroke. However, not all patients on aspirin (ASA) benefit. We studied the phenomenon of aspirin resistance with a simple and reliable platelet function analyzer--the PFA-100. Studying 31 patients with unstable angina and 105 controls, we found aspirin resistance in 42% of patients, most of whom were shown to be compliant utilizing concomitant salicylate levels.     

A study on vascular retinal alterations in patients with coronary artery disease

The paper describes the study carried out on a sample of 27 coronary artery disease patients, aiming to determine a correlation between coronary artery disease and anomalies in the retinal circulation. Patients underwent selective coronary arteriography and fundus fluorescein angiography that allowed us to investigate the dye dynamics and to detect abnormalities of time evolution, vessel walls, and flux. During the fluorescein angiography we measured time events as the choroidal flush (t_a) the start of the laminar phase (t_b), and the end of the laminar phase (t_c) and we took pictures that were digitally processed in order to compute the ROI₁/ROI₂ value, assumed as a numerical index of ischemia of the optic disc. In the examined sample we found t_a=61±109, t_b=65±107, t_c=159±155, and ROI₁/ROI₂=0.968±0.300. Normal ranges for these parameters were determined by the fundus fluorescein angiography of a control group of 10 patients, unaffected by coronary artery disease and ischemic pathology of the retinal network; we found t_a=12±4, t_b=16±8.5, t_c=44±9.3, and ROI₁/ROI₂=0.735±0.086. Eighty-five percent of coronaropatic patients showed ischemia of the optic disc, 89% anomalies of the epi-peripapillar network, 70% anomalies of the papillo-macular network, and 89% evidence of at least two findings of ischemia; 85% of patients showed a value of ROI₁/ROI₂ out of the normal range. The unpaired Student'st-test between the coronaropatic and the control group does not show significant differences between t_a and t_b; on the contrary, those with coronary disease and the control group were statistically different for t_c (p0.02). Moreover, we have found a correlation between the numerical index of optic disc ischemia and the severity of coronary artery disease (r=0.68,p0.01). Hence, the vascular abnormalities shown by the fluorescein angiography can constitute valid noninvasive markers and can advise further cardiological tests for a coronary artery disease not yet diagnosed.     

Ankle-brachial index as a predictor of the extent of coronary atherosclerosis and cardiovascular events in patients with coronary artery disease

Resting ankle-brachial pressure index (ABI) is a noninvasive method to assess the patency of the lower extremity arterial system. This study aimed to examine the relation between ABI and the extent of coronary atherosclerosis, the extracoronary atherosclerosis lesions, and the prognosis of patients referred for elective coronary angiography. One hundred sixty-five consecutive patients underwent coronary angiography, ultrasound imaging for intima-media thickness measurement of carotid and femoral arteries and ABI evaluation; subjects were followed up for 14.5 +/- 2.4 months. With regard to vascular risk factors, only smoking (p = 0.025) and diabetes (p = 0.01) were related to ABI in the multiple regression analysis. ABI was independently and inversely related to carotid bifurcation (p = 0.0002) and common femoral artery intima-media thickness (p = 0.018). ABI was related to the extent of coronary artery disease as measured by number of coronary arteries diseased (analysis of variance, p = 0.04) and Gensini angiographic score (p = 0.01). In the follow-up study ABI < 0.90 was a univariate predictor of cardiovascular events (cardiac death, nonfatal myocardial infarction, unstable angina) and revascularization procedures. The estimated cumulative rate free of cardiovascular events was 90% for ABI > 0.90 and 73% for ABI < 0.90 (p = 0.02). In logistic regression analysis, ABI < 0.90 was an independent predictor for cardiovascular events after adjustment for age, low-density lipoprotein cholesterol, carotid and femoral intima-media thickness, and Gensini score. Further adjustment for the confounding effect of insulin weakened the relation between ABI and cardiovascular events (p = 0.1). In conclusion, ABI is a simple index related to the extent of atherosclerosis in coronary and noncoronary arterial beds, reflecting generalized atherosclerosis. ABI could be useful in assessing the risk for cardiovascular events in patients with coronary artery disease.     

Mast cell tryptase: a new biomarker in patients with stable coronary artery disease

Mast cells may participate actively in the inflammatory process of atherosclerotic plaques by releasing proteolytic enzymes and various other pro-inflammatory substances. We hypothesized that increased levels of mast cell tryptase, could be an important biomarker in patients with stable coronary artery disease (CAD). We measured tryptase in 102 patients without acute coronary syndromes undergoing cardiac catheterization. Patients with significant CAD [> or =50% stenosis in > or =1 artery (n=66)] had significantly higher serum tryptase than patients with normal angiography (n=13) or non-significant CAD [<50% stenosis (n=23)]. The median, 25th and 75th percentiles for tryptase in these two groups were 8.38 (6.4 and 10.7)mug/L versus 6.78 (5.61 and 9.72) microg/L, p=0.014. Patients in the highest quartile of tryptase levels had a 4.3-fold risk for CAD [Odds ratio (OR): 4.3; 95% confidence interval (CI): 1.08-17.19; p=0.04]. In a multivariate regression analysis, tryptase remained an independent predictor for CAD along with age (OR: 1.178; 95% CI: 1.021-1.359, p=0.025). High circulating tryptase levels may be a result of chronic low-grade inflammatory activity present in atherosclerotic plaques. Tryptase measurements may emerge as a novel way of identifying asymptomatic patients with CAD, and represent a new biomarker of therapeutic efficacy in patients with CAD.